The present invention relates to a controlled release pharmaceutical preparation, and more particularly to a so-called sigmoid type controlled release pharmaceutical preparation (Sigmoidal-Releasing System) from which a medicinal compound rapidly dissolves after a certain lag time.
Hitherto, concerning pharmaceutical preparations containing medicinal compounds, there have been various attempts to maintain their effects after the administration. For example, following two pharmaceutical preparations have been known. One is a sustained release pharmaceutical preparation (see Japanese Unexamined Patent Publication No. 156617/1985) in which a core is alternately coated with two compositions, namely, with a coating composition comprising a water-soluble polymer such as a polyvinyl alcohol or polyvinylpyrrolidone and a water-insoluble polymer such as ethylcellulose, polyvinyl chloride or Eudragit RS (trade mark, from Rohm Pharma, Germany), and a composition comprising diltiazem hydrochloride, an organic acid and a lubricant to form multi coating layers. And the other is a sustained release pharmaceutical preparation (see Japanese Unexamined Patent Publication No. 193913/1985) in which a core containing a medicinal active ingredient and an organic acid is spray-coated with an ethanol solution of an acrylic polymer having trimethylammoniumethyl group.
However, although these pharmaceutical preparations are suitable for releasing medicinal active ingredients gradually after the administration, they have a problem that the starting of the dissolution of their medicinal active ingredients can hardly be controlled.
On the other hand, it is known in the field of the pharmaceutical preparation that an increase in the thickness of the coating layer results in a delay of the starting of the dissolution of a medicinal active ingredient. However, it is also known that in this case the thick coat layer hinders rapid dissolution of a medicinal active ingredient after the starting of the dissolution and therefore an effective blood concentration can not be obtained rapidly.
An object of this invention is to provide a controlled release pharmaceutical preparation giving a so-called sigmoid type dissolution pattern wherein a lag time until the starting of the dissolution of a medicinal compound and the rate of the following dissolution can be controlled and the rate of the dissolution of the medicinal compound does not depend on the pH of a medium for the dissolution.
This and other objects of the present invention will become apparent from the description hereinafter.